End-stage renal disease (ESRD) is a devastating illness, and each year in the United States more than 80,000 new patients need initiation of therapy for ESRD. The majority of these patients will receive life-sustaining treatments in the form of hemodialysis. Unfortunately, the quality and duration of the lives of patients on hemodialysis are severely restricted by vascular access. Recent observations suggest that nearly 25% of hospitalizations in the ESRD population are related to vascular access, and problems that emanate from vascular access cost nearly $1 billion annually. Vascular access failure is arguably the most important reversible cause of morbidity in ESRD. This application is in response to RFA DK-00-012 and describes our competence to serve as a clinical center in the Hemodialysis Vascular Access Consortium. We have a strong track record in recruiting for and participating in similar multicenter trials in Nephrology, since we currently serve as large clinical sites for the African American Study of Kidney Disease and Hypertension (AASK) and the Morbidity and Mortality and in Hemodialysis (HEMO) trials. We propose a prevention trial with the cell cycle inhibitor Sirolimus (Rapamycin) in PTFE grafts. We will recruit from our pool of more than 2000 hemodialysis patients, and we will work with the Data Coordinating Center and the other sites to design and conduct a series of multicenter, randomized, placebo-controlled clinical trials of therapies to reduce the complication rate of AV grafts and fistulas in hemodialysis patients over a 5-year period. We anticipate that this consortium will be able to develop new approaches to managing hemodialysis vascular access, and that these new treatments can decrease the costs and complications of hemodialysis care of the US ESRD population.